Immunotherapy Based on Blocking Cell Inhibitory Pathways

Author(s):  
Randy F Sweis ◽  
Jason J Luke
Keyword(s):  
Author(s):  
Chloe Alexandre ◽  
Alban Latremoliere ◽  
Patrick H. Finan

With the advent of modern lifestyles, there has been a significant extension of daily activities, mostly at the cost of sleep. Lack of sleep affects many biological systems, including various cognitive functions, the immune system, metabolism, and pain. Both sleep and pain are complex neurological processes that encompass many dynamic components. As a result, defining the precise interactions between these two systems represents a challenge, especially for chronic paradigms. This chapter describes how sleep is measured and how it can be experimentally altered in humans and animal models, and, in turn, how sleep disturbances, either acute or chronic, can affect different aspects of pain. Possible mechanisms involved are discussed, including an increase in inflammatory processes, a loss of nociceptive inhibitory pathways, and a defect in the cognitive processing of noxious inputs.


2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Florence Steiner ◽  
Marine Bobin ◽  
Sascha Frühholz

AbstractThe temporal voice areas (TVAs) in bilateral auditory cortex (AC) appear specialized for voice processing. Previous research assumed a uniform functional profile for the TVAs which are broadly spread along the bilateral AC. Alternatively, the TVAs might comprise separate AC nodes controlling differential neural functions for voice and speech decoding, organized as local micro-circuits. To investigate micro-circuits, we modeled the directional connectivity between TVA nodes during voice processing in humans while acquiring brain activity using neuroimaging. Results show several bilateral AC nodes for general voice decoding (speech and non-speech voices) and for speech decoding in particular. Furthermore, non-hierarchical and differential bilateral AC networks manifest distinct excitatory and inhibitory pathways for voice and speech processing. Finally, while voice and speech processing seem to have distinctive but integrated neural circuits in the left AC, the right AC reveals disintegrated neural circuits for both sounds. Altogether, we demonstrate a functional heterogeneity in the TVAs for voice decoding based on local micro-circuits.


TH Open ◽  
2020 ◽  
Vol 04 (03) ◽  
pp. e163-e172
Author(s):  
Juergen Koessler ◽  
Philipp Klingler ◽  
Marius Niklaus ◽  
Katja Weber ◽  
Angela Koessler ◽  
...  

Abstract Introduction Cold storage of platelets is considered to contribute to lower risk of bacterial growth and to more efficient hemostatic capacity. For the optimization of storage strategies, it is required to further elucidate the influence of refrigeration on platelet integrity. This study focused on adenosine diphosphate (ADP)-related platelet responsiveness. Materials and Methods Platelets were prepared from apheresis-derived platelet concentrates or from peripheral whole blood, stored either at room temperature or at 4°C. ADP-induced aggregation was tested with light transmission. Activation markers, purinergic receptor expression, and P2Y12 receptor function were determined by flow cytometry. P2Y1 and P2X1 function was assessed by fluorescence assays, cyclic nucleotide concentrations by immunoassays, and vasodilator-stimulated phosphoprotein (VASP)-phosphorylation levels by Western blot analysis. Results In contrast to room temperature, ADP-induced aggregation was maintained under cold storage for 6 days, associated with elevated activation markers like fibrinogen binding or CD62P expression. Purinergic receptor expression was not essentially different, whereas P2Y1 function deteriorated rapidly at cold storage, but not P2Y12 activity. Inhibitory pathways of cold-stored platelets were characterized by reduced responses to nitric oxide and prostaglandin E1. Refrigeration of citrated whole blood also led to the attenuation of induced inhibition of platelet aggregation, detectable within 24 hours. Conclusion ADP responsiveness is preserved under cold storage for 6 days due to stable P2Y12 activity and concomitant disintegration of inhibitory pathways enabling a higher reactivity of stored platelets. The ideal storage time at cold temperature for the highest hemostatic effect of platelets should be evaluated in further studies.


2020 ◽  
Vol Volume 13 ◽  
pp. 1211-1223
Author(s):  
Hao Li ◽  
Xinglan An ◽  
Daoyu Zhang ◽  
Qi Li ◽  
Nan Zhang ◽  
...  
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2007 ◽  
Vol 292 (1) ◽  
pp. R291-R307 ◽  
Author(s):  
Maureen T. Cruz ◽  
Erin C. Murphy ◽  
Niaz Sahibzada ◽  
Joseph G. Verbalis ◽  
Richard A. Gillis

Our primary purpose was to characterize vagal pathways controlling gastric motility by microinjecting l-glutamate into the dorsal motor nucleus of the vagus (DMV) in the rat. An intragastric balloon was used to monitor motility. In 39 out of 43 experiments, microinjection of l-glutamate into different areas of the DMV rostral to calamus scriptorius (CS) resulted in vagally mediated excitatory effects on motility. We observed little evidence for inhibitory effects, even with intravenous atropine or with activation of gastric muscle muscarinic receptors by intravenous bethanechol. Inhibition of nitric oxide synthase with Nω-nitro-l-arginine methyl ester (l-NAME) HCl did not augment DMV-evoked excitatory effects on gastric motility. Microinjection of l-glutamate into the DMV caudal to CS produced vagally mediated gastric inhibition that was resistant to l-NAME. l-Glutamate microinjected into the medial subnucleus of the tractus solitarius (mNTS) also produced vagally mediated inhibition of gastric motility. Motility responses evoked from the DMV were always blocked by ipsilateral vagotomy, while responses evoked from the mNTS required bilateral vagotomy to be blocked. Microinjection of oxytocin into the DMV inhibited gastric motility, but the effect was never blocked by ipsilateral vagotomy, suggesting that the effect may have been due to diffusion of oxytocin to the mNTS. Microinjection of substance P and N-methyl-d-aspartate into the DMV also produced inhibitory effects attributable to excitation of nearby mNTS neurons. Our results do not support previous studies indicating parallel vagal excitatory and inhibitory pathways originating in the DMV rostral to CS. Our results do support previous findings of vagal inhibitory pathways originating in the DMV caudal to CS.


Immunity ◽  
2011 ◽  
Vol 34 (4) ◽  
pp. 616-626 ◽  
Author(s):  
Tanya R. McKitrick ◽  
Christina C. Muscat ◽  
James D. Pierce ◽  
Deepta Bhattacharya ◽  
Anthony W. De Tomaso
Keyword(s):  

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